| Abstract|| |
A 71-year-old female patient was admitted with intractable diarrhea and abdominal distention following several courses of broad spectrum antibiotic therapy. Colonic biopsy revealed pseudomembranous colitis with foci of signet ring cell (SRC) change. The SRCs possessed bland nuclei and were confined to the basement membranes of the crypts with no infiltration into the lamina propria. Benign SRCs in pseudomembranous colitis is an uncommon phenomenon. Awareness of this rare, but potential pitfall is of utmost importance to avoid a misdiagnosis of SRC carcinoma.
Keywords: Colon, pseudomembranous colitis, signet ring cells
|How to cite this article:|
Jacob S, Zayyani NR. Benign signet ring cells in pseudomembranous colitis: A diagnostic trap. Indian J Pathol Microbiol 2013;56:413-5
| Introduction|| |
The presence of signet ring cells (SRCs) in the gastrointestinal tract (GIT) was once considered a diagnostic indicator of signet ring carcinoma.  The phenomenon of benign mucin cells of the GIT rounding up and taking the shape of signet rings after they are damaged and desquamated is not widely known. Schiffman in 1996 was the first to draw attention to the unusual occurrence of benign SRCs in a case of fulminant pseudomembranous colitis.  Since then sporadic cases of SRC change in association with pseudomembranous colitis have been reported in the literature with a total of about 22 cases. ,,,,,,
Benign SRC can easily be confused with SRC carcinoma and lack of awareness of this entity may lead to overdiagnosis and unnecessary radical treatment.  This paper documents an additional case of pseudomembranous colitis with this rather unusual and misleading feature.
| Case Report|| |
A 71-year-old female patient presented with a 3 week history of severe uncontrolled non-bloody diarrhea, abdominal pain, anorexia, nausea and altered mental status. At 3 weeks prior to the onset of these symptoms, she had a fall and became bed-ridden. Owing to her immobilization, she developed severe constipation and was given an enema at another hospital. During the hospitalization, she received several courses of broad spectrum antibiotics for urinary tract infection. At 2 weeks prior to admission to our hospital, she developed severe, non-bloody diarrhea more than fifteen bowel movements per day, abdominal pain and anorexia. Empiric antibiotics were added for diarrhea, but her condition deteriorated with altered mental status and she was transferred to our hospital.
On admission, the patient was febrile, with temperature of 38.5°C and in a confused state. The abdomen was distended and tender without rebound tenderness. Ultrasound and computed tomography of the abdomen revealed diffusely thickened colon with free fluid in the abdomen [Figure 1]. The stools were watery and occult blood positive, but negative for Clostridium difficile toxin.
|Figure 1: (a) Diffuse thickening of wall of sigmoid colon seen in ultrasonogram and (b) computed tomography scan|
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Colonoscopy done showed severe-pseudomembranous colitis throughout the colon [Figure 2]. Multiple biopsies were taken.
Vancomycin, 500 mg starting dose followed by 250 mg 6 hourly was started per nasogastric tube and nutritional support given. In spite of supportive care, the patient deteriorated with Gram-negative septicemia and died on the 7 th hospital day.
|Figure 2: Extensive pseudomembranous exudates within sigmoid colon on colonoscopy|
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The endoscopic colonic biopsies revealed patchy foci of necrosis and explosive inflammatory exudate mushrooming out from breach in the surface epithelium [Figure 3]. The exudate was composed of mucus, fibrin, polymorphonuclear leucocytes and desquamated epithelial cells. In focal areas, the crypts were lined by signet ring shaped cells with abundant pale cytoplasm and peripherally placed bland crescentic nuclei. The nuclei had inconspicuous nucleoli and uniform chromatin and showed no mitotic activity. The SRCs were limited within the boundaries of the cryptal basement membrane with no infiltration of the lamina propria [Figure 4]. These cells were further highlighted by Alcian blue/periodic acid schiff staining [Figure 5]. No fibrosis of the lamina propria was evident.
|Figure 3: Patchy erosions, surface infl ammatory exudates and signet ring cells within crypts (H and E, ×100)|
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|Figure 4: Distended crypts lined by signet ring cells with bland nuclei (arrows) (H and E, ×200)|
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|Figure 5: Signet ring cells within crypts highlighted by Alcian blue/ periodic acid Schiff stain, ×400|
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| Discussion|| |
SRCs are most commonly associated with mucin producing malignant epithelial tumors arising in a variety of sites like stomach, large intestine, appendix, breast, pancreas, urinary bladder and prostate.  Although once considered synonymous with adenocarcinoma, benign SRC change is now known to occur in an expanding list of benign and non-epithelial malignant tumors as well as non-neoplastic processes viz. nodular goiter, malignant thyroid tumors, signet ring lymphoma, clear cell myeloma, lipoblastic meningioma, degenerated lymphocytes, vacuolated smooth muscle cells in transurethral resection of the prostate specimens, within decidua and endometriosis etc. ,,
The GIT is however the most frequent site in which benign SRC has been described. Most of these cases have been reported in association with pseudomembranous colitis. ,,,,,, In a meticulous study of 50 patients with pseudomembranous colitis, Wang et al. noted SRC in 14 patients, the change being extensive only in four.  Of the 22 cases documented in the literature, only five were associated with toxic megacolon. ,,, Besides their association with pseudomembranous colitis, SRC have also been noted in Peutz Jegher' polyp, ulcerated tubular adenoma, gastric ulcer, gastric mucosa-associated lymphoid tissue lymphoma and cholecystitis. ,,,
The pathogenesis of SRC is not clearly elucidated. Some of the authors proposed that in cases of pseudomembranous colitis, presence of SRC may be associated with the severity of the disease, , whereas others found no such link. , Chen postulated that SRC was the result of ischemia, whereas others suggested that it could be related to inflammation. ,
The significance of SRC lies in its differentiation from SRC carcinoma. SRC carcinoma is classically featured by cellular atypia with enlarged hyperchromatic nuclei having prominent nucleoli and increased mitotic activity.  SRC can also be distinguished from those cases of carcinoma with bland nuclear features by the fact that the benign SRC do not occur outside the crypts in the lamina propria, submucosa or muscular coat, but distribute only within the crypt boundaries. , This feature can be highlighted by staining with anticollagen IV and antilaminin antibodies. , In cases where the cryptal basement membrane is not well-preserved, staining with p53, Ki67 and E cadherin will resolve the dilemma. Benign SRC display negative staining with p53 and Ki67 and positivity for E cadherin whereas malignant SRCs are immunoreactive for p53 and Ki67 and show weak or negative E cadherin staining. , Muciphages and xanthoma cells may at times mimic SRCs. Unlike SRCs, they are immunoreactive for CD68 and negative for cytokeratin markers, CAM5.2 and AE1/AE3. ,
To conclude, benign SRC change in the GIT is a potential diagnostic trap for surgical pathologists as it may be misdiagnosed as signet ring carcinoma. This grave error can be avoided by attention to the history, endoscopic findings and microscopic features and more importantly, awareness of this benign, but potential pitfall. , Care must be taken especially in small biopsies and in patients with a previous history of colon carcinoma. ,
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Department of Pathology, Bahrain Specialist Hospital, Juffair, Manama
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]